Possible role of the α7 nicotinic receptors in mediating nicotine's effect on developing lung - implications in unexplained human perinatal death
Possible role of the α7 nicotinic receptors in mediating nicotine's effect on developing lung - implications in unexplained human perinatal death
复制标题
DOI：
10.1186/1471-2466-14-11
复制
发表时间：
2014-02-01
影响因子：
3.1
通讯作者：
Matturri, Luigi
中科院分区：
文献类型：
--
作者：
Lavezzi, Anna M.;Corna, Melissa F.;Matturri, Luigi
背景：众所周知，孕妇孕期吸烟对胎儿危害很大。特别是，产前尼古丁吸收与出生时肺发育和功能的变化以及婴儿时期的呼吸障碍有关。许多肺部疾病是通过尼古丁与尼古丁受体(NAChRs)的相互作用而介导的，尤其是与发育中的肺中广泛表达的α7 nAChR亚单位的相互作用。为了确定母亲吸烟的胎儿和新生儿猝死患者中常见的肺发育不良是否由尼古丁与肺尼古丁受体相互作用所致，我们用免疫组织化学方法研究了α7nAChR亚单位在这些病理过程中的可能存在。方法：在45例死于宫内原因猝死综合征(SIUDS)和15例死于婴儿猝死综合征(SDS)的肺组织切片中，我们应用放射状肺泡计数(RAC)来评估肺成熟程度，并应用免疫组织化学技术检测nAChRs，特别是α7nAChR亚单位的识别。在相同的病例中，对自主神经系统进行了深入的研究，以突出位于大脑的主要生命中心可能的发育变化。结果：根据RAC值低于正常参考值，我们在63%的SIUDS/SIDS病例和8%的对照组中诊断为“肺发育不良”。此外，我们观察到，在母亲吸烟的胎儿和婴儿猝死病例中，肺上皮细胞和肺血管壁中α7 nAChR强免疫染色的发生率显著高于年龄匹配的对照组。患者脑干同时存在中缝核、副面核、Kolliker-Fuse核、弓状核和Botzinger前核团发育不良。结论：尼古丁在穿过胎盘时可与神经细胞和非神经细胞的烟碱受体相互作用，分别导致肺和神经系统发育障碍。这项工作强调了实施可预防措施的重要性，以减少怀孕期间尼古丁的有害潜力。
Background: It is well known that maternal smoking during pregnancy is very harmful to the fetus. Prenatal nicotine absorption, in particular, is associated with alterations in lung development and functions at birth and with respiratory disorders in infancy. Many of the pulmonary disorders are mediated by the interaction of nicotine with the nicotinic receptors (nAChRs), above all with the alpha 7 nAChR subunits that are widely expressed in the developing lung. To determine whether the lung hypoplasia frequently observed in victims of sudden fetal and neonatal death with a smoker mother may result from nicotine interacting with lung nicotinic receptors, we investigated by immunohistochemistry the possible presence of the alpha 7 nAChR subunit overexpression in these pathologies.Methods: In lung histological sections from 45 subjects who died of sudden intrauterine unexplained death syndrome (SIUDS) and 15 subjects who died of sudden infant death syndrome (SIDS), we applied the radial alveolar count (RAC) to evaluate the degree of lung maturation, and the immunohistochemical technique for nAChRs, in particular for the alpha 7 nAChR subunit identification. In the same cases, an in-depth study of the autonomic nervous system was performed to highlight possible developmental alterations of the main vital centers located in the brainstem.Results: We diagnosed a "lung hypoplasia", on the basis of RAC values lower than the normal reference values, in 63% of SIUDS/SIDS cases and 8% of controls. In addition, we observed a significantly higher incidence of strong alpha 7 nAChR immunostaining in lung epithelial cells and lung vessel walls in sudden fetal and infant death cases with a smoker mother than in age-matched controls. Hypoplasia of the raphe, the parafacial, the Kolliker-Fuse, the arcuate and the pre-Botzinger nuclei was at the same time present in the brainstem of these victims.Conclusions: These findings demonstrate that when crossing the placenta, nicotine can interact with nicotinic receptors of both neuronal and non-neuronal cells, leading to lung and nervous system defective development, respectively. This work stresses the importance of implementing preventable measures to decrease the noxious potential of nicotine in pregnancy.